The influence of 6-hydroxydopamine on the development and inducibility of drug metabolism in rat liver.
6-Hydroxydopamine (6-OHDA) pretreatment of rats in the first 4 days of life considerably enhances the low hepatic ethylmorphine N-demethylation rate in 9 and 16 day old rats, whereas the higher rates in adult rats are not influenced. After 6-OHDA treatment the age differences in ethylmorphine N-demethylation rate disappear. The induction of ethylmorphine N-demethylation by phenobarbital is markedly enhanced by neonatal 6-OHDA pretreatment in 16 to 60 day old rats, whereas in 9 day old rats this synergistic action is not detectable. Unlike ethylmorphine N-demethylation, hepatic 7-ethoxy-coumarin 0-deethylation rate is only slightly or not at all influenced by 6-OHDA pretreatment. The basic activities in 9 day and rats are enhanced, the induction by phenobarbital in the same age-group is decreased. In other age-groups neither basic activities nor inducibility are influenced by 6-OHDA pretreatment. Hepatic cytochrome P-450 concentrations in 33- and 60 day old control rats do not differ from those in 6-OHDA-pretreated animals. Phenobarbital treatment increases the P-450 content; this induction effect is enhanced after 6-OHDA pretreatment, but not as markedly as with ethylmorphine N-demethylation.
D000367:Age Factors; D000818:Animals; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains
D006892:Hydroxydopamines; D016627:Oxidopamine; D005037:Ethylmorphine-N-Demethylase